Vimentin S‐glutathionylation at Cys328 inhibits filament elongation and induces severing of mature filaments in vitro

Vimentin intermediate filaments are a significant component of the cytoskeleton in cells of mesenchymal origin. In vivo, filaments assemble and disassemble and thus participate in the dynamic processes of the cell. Posttranslational modifications (PTMs) such as protein phosphorylation regulate the multiphasic association of vimentin from soluble complexes to insoluble filaments and the reverse processes. The thiol side chain of the single vimentin cysteine at position 328 (Cys328) is a direct target of oxidative modifications inside cells. Here, we used atomic force microscopy, electron microscopy and a novel hydrogen–deuterium exchange mass spectrometry (HDex-MS) procedure to investigate the structural consequences of S-nitrosylation and S-glutathionylation of Cys328 for in vitro oligomerisation of human vimentin. Neither modification affects the lateral association of tetramers to unit-length filaments (ULF). However, S-glutathionylation of Cys328 blocks the longitudinal assembly of ULF into extended filaments. Snitrosylation of Cys328 does not hinder but slows down the elongation. Likewise, S-glutathionylation of preformed vimentin filaments causes their extensive fragmentation to smaller oligomeric species. Chemical reduction of the S-glutathionylated Cys328 thiols induces reassembly of the small fragments into extended filaments. In conclusion, our in vitro results suggest Sglutathionylation as a candidate PTM for an efficient molecular switch in the dynamic rearrangements of vimentin intermediate filaments, observed in vivo, in response to changes in cellular redox status. Finally, we demonstrate that HDex-MS is a powerful method for probing the kinetics of vimentin filament formation and filament disassembly induced by PTMs

Toward an understanding of the conformational plasticity of S100A8 and S100A9 Ca2+-binding proteins

S100A8 and S100A9 are small, human, Ca2+-binding proteins with multiple intracellular and extracellular functions in signaling, regulation, and defense. The two proteins are not detected as monomers but form various noncovalent homo- or hetero-oligomers related to specific activities in human physiology. Because of their significant roles in numerous medical conditions, there has been intense research on the conformational properties of various S100A8 and S100A9 proteoforms as essential targets of drug discovery. NMR or crystal structures are currently available only for mutated or truncated protein complexes, mainly with bound metal ions, that may well reflect the proteins' properties outside cells but not in other biological contexts in which they perform. Here, we used structural mass spectrometry methods combined with molecular dynamics simulations to compare the conformations of wildtype full-length S100A8 and S100A9 subunits in biologically relevant homo- and heterodimers and in higher oligomers formed in the presence of calcium or zinc ions. We provide, first, rationales for their functional response to changing environmental conditions, by elucidating differences between proteoforms in flexible protein regions that may provide the plasticity of the binding sites for the multiple targets, and second, the key factors contributing to the variable stability of the oligomers. The described methods and a systematic view of the conformational properties of S100A8 and S100A9 complexes provide a basis for further research to characterize and modulate their functions for basic science and therapies

Trends in hypertension prevalence, awareness, treatment, and control among Polish adults 75 years and older during 2007–2014

Background: The aim of this study was to assess changes in the prevalence, awareness, and treatment of hypertension and its effectiveness between 2007 (WOBASZ Senior study) and 2013–2014 (WOBASZ II) in a sample of the Polish population over the age of 75 years. Methods: Sampling had three stages, stratified according to voivodeships, type of community, and gen­der. Finally, the WOBASZ II study included 467 persons (290 women and 177 men). For a comparison of the data, 1096 persons (538 women and 554 men) examined in the WOBASZ Senior study were used. Results: Systolic and diastolic blood pressures significantly decreased from 153.0 ± 23.9 mmHg to 142.9 ± 22.3 mmHg and from 85.2 ± 11.9 mmHg to 78.4 ± 11.3 mmHg, respectively, from 2007 to 2014 (p < 0.0001). Prevalence of hypertension among people included in WOBASZ studies slightly decreased from 83.8% to 77.9% (rate ratio [RR]: 0.95; 95% confidence interval [CI]: 0.78–1.16) in men, and from 75.4% to 71.8% (RR: 0.93; 95% CI: 0.8–1.09) in women. Hypertension awareness was improved from 59.2% to 72.9% (RR: 1.23; 95% CI: 0.97–1.56) in men, and from 74,8% to 93% (RR: 1.26; 95% CI: 1.01–1.58) in women. The proportion of men and women, with implemented hypertension treatment, increased from 48.4% to 61.1% (RR: 1.26; 95% CI: 1.01–1.58), and from 63.2% to 82.0% (RR: 1.3; 95% CI: 1.1–1.53), respectively. The effectiveness of the treatment was improved over two-fold, there was an increase from 10.3% to 26.8% (RR: 2.65; 95% CI: 1.81–3.89) in men, and from 13.8% to 33.5% in women (RR: 2.44; 95% CI: 1.81–3.3). Conclusions: The prevalence of hypertension in Polish seniors remains high, but has decreased slightly in the perspective of the last 7 years. Although treatment and control has improved over the last decade, it remains below expectations. Efforts to improve the diagnosis and effective treatment of hypertension in Polish seniors should be intensified

Prevalence, awareness, treatment and control of hypertension in the adult Polish population : multi-center National Population Health Examination Surveys : WOBASZ studies

Introduction: Hypertension is one of the main risk factors of cardiovascular diseases. The first aim of the study was to evaluate the prevalence, awareness and treatment of hypertension as well as treatment effectiveness (blood pressure < 140/90 mm Hg) in a representative sample of the Polish population over the age of 19, examined in the WOBASZ II program. The second aim was to assess the changes in these parameters between 2003-2005 (WOBASZ study) and 2013-2014 in adults aged 20-74. Material and methods: Sampling was performed in three stages, stratified according to voivodeship (province), type of commune, and gender. Finally, the study included 6163 persons (3406 women and 2757 men) examined in the years 2013-2014 (aged ≥ 19 years). For comparison the data from 14 755 persons (7783 women and 6452 men aged 20-74 years) examined in the years 2003-2005 were used. Results: In the years 2013-2014, the age-standardized prevalence of hypertension, awareness, treatment and control was 42.7%, 59.3%, 46.1%, and 23% respectively. In the last decade an increase in the prevalence of hypertension (relative ratio (RR) 1.12; 95% confidence interval (CI): 1.07- 1.18), treatment (RR = 1.26; 95% CI: 1.17-1.36) and control (RR = 2.16; 95% CI: 1.91-2.45) was found. In contrast, the awareness decreased nonsignificantly (RR = 0.98; 95% CI: 0.92-1.05). Conclusions: The prevalence of hypertension in Poland is high, and increased by about 12% in 10 years. Although the number of treated patients and blood pressure control improved nearly twofold over the last decade, this is still below expectations. Efforts to improve the diagnosis and effective treatment of hypertension in Poland should still be intensifie

Sleep deficiency among LS Aiport Secices SA shift workers on Chopin Aiport in Warsaw.

Niniejsza praca ma na celu przeprowadzenie analizy chronobiologicznych parametrów snu, dokonanie subiektywnej oceny problemów ze snem u pracowników zmianowych obsługi naziemnej LS Aiport Services S.A. jest również próbą korelacji pomiędzy chronotypem a deprywacją snu. Pokazały również, jak bardzo niedobór snu wpływa na brak koncentracji. Z przeprowadzonych badań nie wynika jednak by chronotyp badanych powodował ograniczenia związane z deficytem snu. Praca w systemie zmianowym ma istotny wpływ na zaburzenia rytmów okołodobowych. Pamiętać należy, że na jakość snu oprócz pracy zmianowej może mieć wpływ wiele innych czynników, miedzy innymi nadmierna aktywność fizyczna, stres oraz choroby somatyczne. Współdziałanie kilku czynników może zwiększać zmęczenie i wymagać większej ilości snu i odpoczynku.This paper aims to analyze the chronobiological sleep factor and to make a subjective assessment of sleep problems among LS Aiport Sevices SA shift workers.It is also an attempt to show a correlation between a chronotype and sleep deprivation .The study does not itself show, however, that the respondents chronotyp caused limitations associated with sleep deficiency.Shift work has a significant impact on disordes of circadian rhythms.It should be remembered that the quality of sleep, besides shift work, can be influenced by many factors, including excessive physical activity, stress and somatic disorders.Interaction of several factors may increase and may require more sleep and rest

Drugs modulating the L-arginine:NO:cGMP pathway – current use in therapy

Nitric oxide (NO) is a relatively novel messenger that plays a significant role in a wide range of physiological processes. Currently, it is known that, both, lack and excess of NO can cause diseases, thus a lot of substances have been discovered and utilized which can change the concentration of this molecule within the organism. The aim of the present work is to provide an overview of currently used agents modulating the L-arginine:NO:cGMP pathway, as well as to summarize current understanding of their pharmacological profiles. Nowadays, most of these agents are employed particularly in the treatment of cardiovascular diseases. Further studies can hold promise for enhancing the therapeutic equipment for a variety of other impairments, such as osteoporosis, and also in treatments of the central nervous system

ANTINOCICEPTIVE AND ANTIANXIETY ACTIVITY OF HYDROETHANOLIC EXTRACTS OF THREE IMPATIENS SPECIES IN MICE

The plants of the Impatiens L. (Balsaminaceae) have been used for a long time in folk medicine in different painful conditions, and to treat rheumatism, isthmus and crural aches, fractures, superficial infections, fingernail inflammation. This study was undertaken to determine the pharmacological profile of hydroethanolic extracts from Impatiens glandulifera, I. noli-tangere and I. parviflora. A range of behavioral assessments was applied to evaluate the effects of obtained extracts i.e. measurement of body temperature, tests of locomotor activity and motor coordination, nociceptive reaction and anxiety-like behavior. Hydroethanolic extracts were analyzed for total polyphenol (TPC), flavonoid (TFC), flavones/flavonols (TFFC), and flavonones/dihydroflavonols (TFDC) content. Our results show that the extracts from Impatiens species contain high levels of TPC, TFC, TFFC, and TFDC. Oral (i.e., by gavage) administration of Impatiens L. extracts (except for I. noli-tangere) presented an antinociceptive or/and anti-inflammatory activity in the writhing test. The antinociceptive effect of I. parviflora leaves (100 mg/kg) and I. glandulifera flowers (100 mg/kg) was reversed by naloxone. I. glandulifera flowers and roots extracts (100 mg/kg) increased the reaction time to the thermal stimulus in the hot-plate test. All extracts from I. glandulifera (100 mg/kg) showed antianxiety effect in the elevated plus-maze test. It is worth noting that none of the extracts, at the highest used dose – 0.1 ED50 (200 mg/kg), caused coordination impairments or myorelaxation as measured in the rota-rod and chimney tests. These results seem to suggest that the tested extracts are not neurotoxic

Synergistic Action of Sodium Selenite with some Antidepressants and Diazepam in Mice

Background: The antidepressant and anxiolytic effects of selenium (Se) have been proven in many studies. This work was aimed at confirming these activities of its inorganic form&#8212;sodium selenite&#8212;and examining the possible synergy of action with antidepressants and diazepam. Methods: The antidepressant- and anxiolytic-like activity of Se was assessed using forced swim tests (FSTs) and elevated plus-maze test (EPMs). Spontaneous locomotor activity was measured using photoresistor actimeters. The experiments were conducted on male Albino Swiss mice. Results: Sodium selenite (0.5 mg/kg) reduced the immobility time in the FSTs and extended time spent in the open arms of EPMs without affecting locomotor activity The combined administration of Se at an ineffective dose (0.25 mg/kg) together with imipramine (15 mg/kg), fluoxetine (5 mg/kg), tianeptine (10 mg/kg), but not with reboxetine (2.5 mg/kg), resulted in a reduction of immobility time in FSTs, and with a threshold dose of diazepam (0.25 mg/kg) led to the prolongation of time spent in the open arms of the EPM. Moreover, the antidepressant-like effect of Se (0.5 mg/kg) was significantly reduced by pretreatment with p-chlorophenylalanine (100 mg/kg). Conclusions: The results may indicate the participation of serotonergic transmission to antidepressant action of Se and GABA-ergic transmission to its anxiolytic effects